Methyl iodide → 2-Chloro-7,7-difluoro-9-isopropyl-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

Temperature

0 °C

2-chloro-7,7-difluoro-9-isopropyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one (0.800 g, 2.89 mmol) was dissolved in DMA (7 mL) and cooled to 0° C. under nitrogen. NaH (140 mg, 3.50 mmol) was added, the mixture was stirred for 20 min and MeI (0.23 mL, 3.61 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 1 h and quenched with water (25 mL). The pH was adjusted to 1 (aq. HCl) and the mixture was extracted with ethyl acetate (4×20 mL). The comb organic extracts were concentrated in vacuo, dissolved in dichloromethane/trifluoroacetic acid (5:1, 6 ml) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (80 g SiO2, hexanes:ethyl acetate 1:1) to afford the title compound as a yellow solid (0.753 g, 90%).

1. stirringThe reaction mixture was stirred at room temperature for 1 h
2. customquenched with water (25 mL)
3. extractionthe mixture was extracted with ethyl acetate (4×20 mL)
4. concentrationThe comb organic extracts were concentrated in vacuo
5. dissolutiondissolved in dichloromethane/trifluoroacetic acid (5:1, 6 ml)
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash column chromatography on silica gel (80 g SiO2, hexanes:ethyl acetate 1:1)

ORD record

ord-ef0680ec7133454a8d93dd1b365bf710

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08026234B2